tbuckley/cabot-search huggingface dataset:
Long-term outcomes of allogeneic stem cell transplant in multiple myeloma
Authors: Walker M. Schmidt, Nirosha D. Perera, Francis K. Buadi, Suzanne R. Hayman, Shaji K. Kumar, Angela Dispenzieri, David Dingli, Joselle Cook, Martha Q. Lacy, Prashant Kapoor, Nelson Leung, Eli Muchtar, Rahma M. Warsame, Taxiarchis Kourelis, Moritz Binder, Wilson I. Gonsalves, William J. Hogan, Morie A. Gertz
Journal: Blood Cancer Journal (2023)

Abstract Allogeneic stem cell transplant (allo SCT) for multiple myeloma (MM) is potentially curative in some, while toxic in many others. We retrospectively analyzed 85 patients diagnosed with MM who underwent allo SCT as frontline or salvage therapy between 2000 and 2022 at Mayo Clinic Rochester and examined patient outcomes and prognostic markers. Overall survival (OS), progression free survival (PFS), treatment related mortality (TRM), and relapse rates (RR) were estimated using the Kaplan Meier method and competing risk models. Median follow-up was 11.5 years. Median OS and PFS were 1.7 and 0.71 years, respectively. Five-year OS and PFS were 22.2% and 15.1%, respectively. One-year TRM was 23.5%. Twelve patients demonstrated durable overall survival, living 10+ years beyond their allo SCT. This subgroup was more likely to have no or one prior auto SCT ( p = 0.03) and to have been transplanted between 2000 and 2010 ( p = 0.03). Outcomes were poor in this cohort with long follow-up, with few patients surviving 5 years or more, and most relapsing or dying within 2 years. We would expect better outcomes and tolerability with an expanded array of novel therapeutics and would prefer them to allo SCT.
Metabolic PET/CT analysis of aggressive Non-Hodgkin lymphoma prior to Axicabtagene Ciloleucel CAR-T infusion: predictors of progressive disease, survival, and toxicity
Authors: William G. Breen, Jason R. Young, Matthew A. Hathcock, Roman O. Kowalchuk, Matthew P. Thorpe, Radhika Bansal, Arushi Khurana, N. Nora Bennani, Jonas Paludo, Jose Villasboas Bisneto, Yucai Wang, Stephen M. Ansell, Jennifer L. Peterson, Patrick B. Johnston, Scott C. Lester, Yi Lin
Journal: Blood Cancer Journal (2023)

PET/CT is used to evaluate relapsed/refractory non-Hodgkin lymphoma (NHL) prior to chimeric antigen receptor T-cell (CAR-T) infusion at two time points: pre-leukapheresis (pre-leuk) and pre-lymphodepletion chemotherapy (pre-LD). We hypothesized that changes in PET/CT between these time points predict outcomes after CAR-T. Metabolic tumor volume (MTV), total lesion glycolysis (TLG), and other metrics were calculated from pre-leuk and pre-LD PET/CT scans in patients with NHL who received axicabtagene ciloleucel, and assessed for association with outcomes. Sixty-nine patients were analyzed. While single time point PET/CT characteristics were not associated with risk of PD or death, increases from pre-leuk to pre-LD in parenchymal MTV, nodal MTV, TLG of the largest lesion, and total number of lesions were associated with increased risk of death (p < 0.05 for all). LASSO analysis identified increasing extranodal MTV and increasing TLG of the largest lesion as strong predictors of death (AUC 0.74). Greater pre-LD total MTV was associated with higher risk of grade 3+ immune effector cell-associated neurotoxicity syndrome (ICANS) (p = 0.042). Increasing metabolic disease burden during CAR-T manufacturing is associated with increased risk of progression and death. A two variable risk score stratifies prognosis prior to CAR-T infusion and may inform risk-adapted strategies.
Physical exercise reverses immuno-cold tumor microenvironment via inhibiting SQLE in non-small cell lung cancer
Authors: Zhi-Wen Luo, Ya-Ying Sun, Wei Xia, Jun-Ying Xu, Dong-Jing Xie, Chun-Meng Jiao, Ji-Ze Dong, Hui Chen, Ren-Wen Wan, Shi-Yi Chen, Jie Mei, Wen-Jun Mao
Journal: Military Medical Research (2023)
How the FDA approved an antipsychotic that failed to show a meaningful benefit but raised the risk of death
Authors: Robert Whitaker
Journal: BMJ (2023)

In trials, brexpiprazole failed to provide a clinically meaningful benefit and it increased mortality, but the FDA fast tracked its approval and the sponsor predicts $1bn in annual sales. <b>Robert Whitaker</b> investigates the first licensed antipsychotic for treating agitation in elderly patients with dementia
Prognostic value of integrative genomic approaches for IDH-mutant gliomas
Authors: Marco Gallo
Journal: Neuro-Oncology (2023)

Journal Article Prognostic value of integrative genomic approaches for IDH-mutant gliomas Get access Marco Gallo Marco Gallo Department of Pediatrics, Section of Hematology-Oncology, Baylor College of Medicine, Houston, Texas, USATexas Children's Cancer Center, Texas Children's Hospital, Houston, Texas, USA Corresponding Author: Marco Gallo, PhD, 1102 Bates Avenue, Texas Children's Hospital, Houston, TX 77030, USA (marco.gallo@bcm.edu). https://orcid.org/0000-0002-8451-8207 Search for other works by this author on: Oxford Academic PubMed Google Scholar Neuro-Oncology, Volume 25, Issue 11, November 2023, Pages 2042–2043, https://doi.org/10.1093/neuonc/noad151 Published: 17 August 2023 Article history Published: 17 August 2023 Corrected and typeset: 31 August 2023
Immune response after pig-to-human kidney xenotransplantation: a multimodal phenotyping study
Authors: Alexandre Loupy, Valentin Goutaudier, Alessia Giarraputo, Fariza Mezine, Erwan Morgand, Blaise Robin, Karen Khalil, Sapna Mehta, Brendan Keating, Amy Dandro, Anaïs Certain, Pierre-Louis Tharaux, Navneet Narula, Renaud Tissier, Sébastien Giraud, Thierry Hauet, Harvey I Pass, Aurélie Sannier, Ming Wu, Adam Griesemer, David Ayares, Vasishta Tatapudi, Jeffrey Stern, Carmen Lefaucheur, Patrick Bruneval, Massimo Mangiola, Robert A Montgomery
Journal: The Lancet (2023)
Comparative diagnostic yield of different endoscopic techniques for tissue sampling of upper gastrointestinal subepithelial lesions: a network meta-analysis
Authors: Antonio Facciorusso, Stefano Francesco Crinò, Alessandro Fugazza, Silvia Carrara, Marco Spadaccini, Matteo Colombo, Daryl Ramai, Benedetto Mangiavillano, Saurabh Chandan, Paraskevas Gkolfakis, Babu Mohan, Cesare Hassan, Alessandro Repici
Journal: Endoscopy (2023)

Abstract Background There is limited evidence on the comparative diagnostic performance of endoscopic tissue sampling techniques for subepithelial lesions. We performed a systematic review with network meta-analysis to compare these techniques. Methods A systematic literature review was conducted for randomized controlled trials (RCTs) comparing the sample adequacy and diagnostic accuracy of bite-on-bite biopsy, mucosal incision-assisted biopsy (MIAB), endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), and EUS-guided fine-needle biopsy (FNB). Results were expressed as relative risk (RR) and 95%CI. Results Eight RCTs were identified. EUS-FNB was significantly superior to EUS-FNA in terms of sample adequacy (RR 1.20 [95%CI 1.05–1.45]), whereas none of the other techniques significantly outperformed EUS-FNA. Additionally, bite-on-bite biopsy was significantly inferior to EUS-FNB (RR 0.55 [95%CI 0.33–0.98]). Overall, EUS-FNB appeared to be the best technique (surface under cumulative ranking [SUCRA] score 0.90) followed by MIAB (SUCRA 0.83), whereas bite-on-bite biopsy showed the poorest performance. When considering lesions &lt;20 mm, MIAB, but not EUS-FNB, showed significantly higher accuracy rates compared with EUS-FNA (RR 1.68 [95%CI 1.02–2.88]). Overall, MIAB ranked as the best intervention for lesions &lt;20 mm (SUCRA score 0.86 for adequacy and 0.91 for accuracy), with EUS-FNB only slightly superior to EUS-FNA. When rapid on-site cytological evaluation (ROSE) was available, no difference between EUS-FNB, EUS-FNA, and MIAB was observed. Conclusion EUS-FNB and MIAB appeared to provide better performance, whereas bite-on-bite sampling was significantly inferior to the other techniques. MIAB seemed to be the best option for smaller lesions, whereas EUS-FNA remained competitive when ROSE was available.
Sphingosine‐1‐Phosphate Receptor Targeted PLGA Nanobubbles for Inflammatory Vascular Endothelial Cell Catching
Authors: Jian Tang, Yang Liu, Mingxi Li, Xiao Wang, Anning Du, Ning Gu, Fang Yang
Journal: Advanced Healthcare Materials (2023)

Vascular inflammation is an early manifestation and common pathophysiological basis of numerous cardiovascular and cerebrovascular diseases. However, effective surveillance methods are lacking. In this study, sulfur hexafluoride (SF6 )-loaded polylactic acid-co-glycolic acid (PLGA) nanobubbles (NBs) with a surface assembly of cyclodextrin (CD) and sphingosine-1-phosphate (S1P) (S1P@CD-PLGA NBs) are designed. The characterization results show that S1P@CD-PLGA NBs with diameters of ≈200 nm have good stability, biosafety, and ultrasound imaging-enhancement effects. When interacting with inflammatory vascular endothelial cells, S1P molecules encapsulated in cyclodextrin cavities exhibit a rapid, excellent, and stable targeting effect owing to their specific interaction with the highly expressed S1P receptor 1 (S1PR1) on the inflammatory vascular endothelial cells. Particularly, the S1P-S1PR1 interaction further activates the downstream signaling pathway of S1PR1 to reduce the expression of tumor necrosis factor-α (TNF-α) to protect endothelial cells. Furthermore, mouse models of carotid endothelial injuries and mesenteric thrombosis demonstrate that S1P@CD-PLGA NBs have excellent capabilities for in vivo targeting imaging. In summary, this study proposes a new strategy of using S1P to target inflammatory vascular endothelial cells while reducing the expression of TNF-α, which has the potential to be utilized in the targeted surveillance and treatment of vascular inflammatory diseases.
Subgroups of children with Kawasaki disease: a data-driven cluster analysis
Authors: Hao Wang, Chisato Shimizu, Emelia Bainto, Shea Hamilton, Heather R Jackson, Diego Estrada-Rivadeneyra, Myrsini Kaforou, Michael Levin, Joan M Pancheri, Kirsten B Dummer, Adriana H Tremoulet, Jane C Burns
Journal: The Lancet Child & Adolescent Health (2023)

Although Kawasaki disease is commonly regarded as a single disease entity, variability in clinical manifestations and disease outcome has been recognised. We aimed to use a data-driven approach to identify clinical subgroups.We analysed clinical data from patients with Kawasaki disease diagnosed at Rady Children's Hospital (San Diego, CA, USA) between Jan 1, 2002, and June 30, 2022. Patients were grouped by hierarchical clustering on principal components with k-means parcellation based on 14 variables, including age at onset, ten laboratory test results, day of illness at the first intravenous immunoglobulin infusion, and normalised echocardiographic measures of coronary artery diameters at diagnosis. We also analysed the seasonality and Kawasaki disease incidence from 2002 to 2019 by subgroup. To explore the biological underpinnings of identified subgroups, we did differential abundance analysis on proteomic data of 6481 proteins from 32 patients with Kawasaki disease and 24 healthy children, using linear regression models that controlled for age and sex.Among 1016 patients with complete data in the final analysis, four subgroups were identified with distinct clinical features: (1) hepatobiliary involvement with elevated alanine transaminase, gamma-glutamyl transferase, and total bilirubin levels, lowest coronary artery aneurysm but highest intravenous immunoglobulin resistance rates (n=157); (2) highest band neutrophil count and Kawasaki disease shock rate (n=231); (3) cervical lymphadenopathy with high markers of inflammation (erythrocyte sedimentation rate, C-reactive protein, white blood cell, and platelet counts) and lowest age-adjusted haemoglobin Z scores (n=315); and (4) young age at onset with highest coronary artery aneurysm but lowest intravenous immunoglobulin resistance rates (n=313). The subgroups had distinct seasonal and incidence trajectories. In addition, the subgroups shared 211 differential abundance proteins while many proteins were unique to a subgroup.Our data-driven analysis provides insight into the heterogeneity of Kawasaki disease, and supports the existence of distinct subgroups with important implications for clinical management and research design and interpretation.US National Institutes of Health and the Irving and Francine Suknow Foundation.
Pituitary adenoma or neuroendocrine tumour: the need for an integrated prognostic classification
Authors: Ken K. Y. Ho, Ursula B. Kaiser, Phillippe Chanson, Monica Gadelha, John Wass, Lynnette Nieman, Andrew Little, Manish K. Aghi, Lori Raetzman, Kalmon Post, Gerald Raverot, Alexander D. Borowsky, Dana Erickson, Justo P. Castaño, Edward R. Laws, Maria Chiara Zatelli, Jill Sisco, Laura Esserman, Kevin C. J. Yuen, Martin Reincke, Shlomo Melmed
Journal: Nature Reviews Endocrinology (2023)
Long-Term Follow-Up of Interstitial Lung Abnormality: Implication in Follow-Up Strategy and Risk Thresholds
Authors: Sohee Park, Jooae Choe, Hye Jeon Hwang, Han Na Noh, Young Ju Jung, Jung-Bok Lee, Kyung-Hyun Do, Eun Jin Chae, Joon Beom Seo
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

Rationale: The optimal follow-up computed tomography (CT) interval for detecting the progression of interstitial lung abnormality (ILA) is unknown. Objectives: To identify optimal follow-up strategies and extent thresholds on CT relevant to outcomes. Methods: This retrospective study included self-referred screening participants aged 50 years or older, including nonsmokers, who had imaging findings relevant to ILA on chest CT scans. Consecutive CT scans were evaluated to determine the dates of the initial CT showing ILA and the CT showing progression. Deep learning–based ILA quantification was performed. Cox regression was used to identify risk factors for the time to ILA progression and progression to usual interstitial pneumonia (UIP). Measurements and Main Results: Of the 305 participants with a median follow-up duration of 11.3 years (interquartile range, 8.4–14.3 yr), 239 (78.4%) had ILA on at least one CT scan. In participants with serial follow-up CT studies, ILA progression was observed in 80.5% (161 of 200), and progression to UIP was observed in 17.3% (31 of 179), with median times to progression of 3.2 years (95% confidence interval [CI], 3.0–3.4 yr) and 11.8 years (95% CI, 10.8–13.0 yr), respectively. The extent of fibrosis on CT was an independent risk factor for ILA progression (hazard ratio, 1.12 [95% CI, 1.02–1.23]) and progression to UIP (hazard ratio, 1.39 [95% CI, 1.07–1.80]). Risk groups based on honeycombing and extent of fibrosis (1% in the whole lung or 5% per lung zone) showed significant differences in 10-year overall survival (P = 0.02). Conclusions: For individuals with initially detected ILA, follow-up CT at 3-year intervals may be appropriate to monitor radiologic progression; however, those at high risk of adverse outcomes on the basis of the quantified extent of fibrotic ILA and the presence of honeycombing may benefit from shortening the interval for follow-up scans.
TAL1 hijacks MYCN enhancer that induces MYCN expression and dependence on mevalonate pathway in T-cell acute lymphoblastic leukemia
Authors: Shi Hao Tan, Tze King Tan, Rui Yokomori, Minghui Liao, Xiao Zi Huang, Allen Eng Juh Yeoh, Takaomi Sanda
Journal: Leukemia (2023)
Myelodysplastic neoplasm-associated U2AF1 mutations induce host defense defects by compromising neutrophil chemotaxis
Authors: Natalia J. Gurule, Kenneth C. Malcolm, Chelsea Harris, Jennifer R. Knapp, Brian P. O’Connor, Jazalle McClendon, William J. Janssen, Frank Fang Yao Lee, Caitlin Price, Jackson Osaghae-Nosa, Emily A. Wheeler, Christine M. McMahon, Eric M. Pietras, Daniel A. Pollyea, Scott Alper
Journal: Leukemia (2023)

Myelodysplastic neoplasm (MDS) is a hematopoietic stem cell disorder that may evolve into acute myeloid leukemia. Fatal infection is among the most common cause of death in MDS patients, likely due to myeloid cell cytopenia and dysfunction in these patients. Mutations in genes that encode components of the spliceosome represent the most common class of somatically acquired mutations in MDS patients. To determine the molecular underpinnings of the host defense defects in MDS patients, we investigated the MDS-associated spliceosome mutation U2AF1-S34F using a transgenic mouse model that expresses this mutant gene. We found that U2AF1-S34F causes a profound host defense defect in these mice, likely by inducing a significant neutrophil chemotaxis defect. Studies in human neutrophils suggest that this effect of U2AF1-S34F likely extends to MDS patients as well. RNA-seq analysis suggests that the expression of multiple genes that mediate cell migration are affected by this spliceosome mutation and therefore are likely drivers of this neutrophil dysfunction.
Perioperative Chemoimmunotherapy With Durvalumab for Muscle-Invasive Urothelial Carcinoma: Primary Analysis of the Single-Arm Phase II Trial SAKK 06/17
Authors: Richard Cathomas, Sacha I. Rothschild, Stefanie Hayoz, Lukas Bubendorf, Berna C. Özdemir, Bernhard Kiss, Andreas Erdmann, Stefanie Aeppli, Nicolas Mach, Räto T. Strebel, Boris Hadaschik, Dominik Berthold, Hubert John, Deborah Zihler, Mathias Schmid, Ilaria Alborelli, Martina Schneider, Jana Musilova, Martin Spahn, Ulf Petrausch
Journal: Journal of Clinical Oncology (2023)

PURPOSE The integration of immunotherapy in the perioperative setting of muscle-invasive urothelial carcinoma (MIUC) appears promising. SAKK 06/17 investigated the addition of neoadjuvant durvalumab to gemcitabine/cisplatin (GC) chemotherapy followed by radical surgery and adjuvant checkpoint inhibition with durvalumab. PATIENTS AND METHODS SAKK 06/17 was an investigator-initiated, open-label, single-arm phase II study including cisplatin-fit patients with stage cT2-T4a cN0-1 operable MIUC. Four cycles of neoadjuvant GC in combination with four cycles of durvalumab (start with GC cycle 2) were administered, followed by radical surgery. Adjuvant durvalumab was given for 10 cycles. The primary end point was event-free survival (EFS) at 2 years. RESULTS Sixty one patients were accrued at 12 sites. The full analysis set consisted of 57 patients, 54 (95%) had bladder cancer. Median follow-up was 40 months. The primary end point was met, with EFS at 2 years of 76% (one-sided 90% CI [lower bound], 67%; two-sided 95% CI, 62 to 85). EFS at 3 years was 73% (95% CI, 59 to 83). Complete pathologic response in resected patients (N = 52) was achieved in 17 patients (33%), and 31 (60%) had pathologic response &lt;ypT2 ypN0. Overall survival (OS) was 85% (95% CI, 72 to 92) at 2 years and 81% (95% CI, 67 to 89) at 3 years. Grade 3 and 4 treatment-related adverse events (TRAEs) during neoadjuvant treatment occurred in 42% and 25%, respectively. TRAEs related to adjuvant durvalumab were grade 3 in 5 (11%) and grade 4 in 2 (4%) patients. CONCLUSION The addition of perioperative durvalumab to the standard of care for patients with resectable MIUC results in a high EFS and OS at 2 years.
NHS cancer targets are slimmed down with the aim of speeding up diagnoses
Authors: Adrian O’Dowd
Journal: BMJ (2023)

The current 10 cancer targets in the NHS in England are to be slimmed down to just three "standards" from later this year in a move designed to speed up diagnosis times and improve cancer care. Health experts and some politicians have reacted cautiously, welcoming the prospect of quicker diagnoses, but voicing concerns that the changes may be merely "moving the goalposts" on targets and ignoring more widespread problems of overall NHS capacity as waiting numbers remain stubbornly high. NHS England confirmed on 17 August that it was reforming its cancer standards to reflect what mattered to patients and to align with modern clinical practice. Following consultation and engagement with clinical experts and cancer charities, the current 10 performance standards will be consolidated into three key standards:
Preparation of an Ultrahigh-DAR PDL1 monoclonal antibody-polymeric-SN38 conjugate for precise colon cancer therapy
Authors: Honglei Zhang, Jiali Sun, Yu Zhang, Zhenqian Zhang, Xiaoshuang Wang, Zhilin Liu, Xuefei Zhang, Zhaohui Tang, Xuesi Chen
Journal: Biomaterials (2023)
Implementation of a gene therapy education initiative by the ASGCT and Muhimbili University of Health and Allied Sciences
Authors: Kenneth Cornetta, Samantha Kay, Florence Urio, Irene Kida Minja, Erasto Mbugi, Josephine Mgaya, Teddy Mselle, Siana Nkya, Mohamed Zahir Alimohamed, Kinuma Ndaki, Martín Bonamino, Richard C. Koya, Lesha D. Shah, Johnny Mahlangu, Daniela Drago, Savita Rangarajan, Giridhara Rao Jayandharan
Journal: Molecular Therapy (2023)

There has been rapid growth in gene therapy development with an expanding list of approved clinical products. Several therapies are particularly relevant to patients in low- and middle-income countries. Moreover, investing in research and manufacturing presents an opportunity for economic development. To increase awareness of gene therapy, the American Society of Gene and Cell Therapy partnered with the Muhimbili University of Health and Allied Sciences, Tanzania, to create a certificate-bearing course. The goal was to provide faculty teaching in graduate and medical schools with the tools needed to add gene therapy to the university curriculum. The first virtual course was held in October of 2022, and 45 individuals from 9 countries in Africa completed the training. The content was new to approximately two-thirds of participants, with the remaining third indicating that the course increased their knowledge base. The program was well received and will be adapted for other under-resourced regions. There has been rapid growth in gene therapy development with an expanding list of approved clinical products. Several therapies are particularly relevant to patients in low- and middle-income countries. Moreover, investing in research and manufacturing presents an opportunity for economic development. To increase awareness of gene therapy, the American Society of Gene and Cell Therapy partnered with the Muhimbili University of Health and Allied Sciences, Tanzania, to create a certificate-bearing course. The goal was to provide faculty teaching in graduate and medical schools with the tools needed to add gene therapy to the university curriculum. The first virtual course was held in October of 2022, and 45 individuals from 9 countries in Africa completed the training. The content was new to approximately two-thirds of participants, with the remaining third indicating that the course increased their knowledge base. The program was well received and will be adapted for other under-resourced regions.
<i>APC</i>and<i>P53</i>mutations synergise to create a therapeutic vulnerability to NOTUM inhibition in advanced colorectal cancer
Authors: Yuhua Tian, Xin Wang, Zvi Cramer, Joshua Rhoades, Katrina N. Estep, Xianghui Ma, Stephanie Adams-Tzivelekidis, Bryson W. Katona, F Brad Johnson, Zhengquan Yu, M Andres Blanco, Christopher J Lengner, Ning Li
Journal: Gut (2023)

Colorectal cancer (CRC) is a leading cause of cancer-related deaths, with the majority of cases initiated by inactivation of the APC tumour suppressor. This results in the constitutive activation of canonical WNT pathway transcriptional effector ß-catenin, along with induction of WNT feedback inhibitors, including the extracellular palmitoleoyl-protein carboxylesterase NOTUM which antagonises WNT-FZD receptor-ligand interactions. Here, we sought to evaluate the effects of NOTUM activity on CRC as a function of driver mutation landscape.